Perioperative anticoagulation in head and neck free flap reconstructions: Experience of an anticoagulative scheme and its modification.

OBJECTIVES: Microvascular anastomoses in microvascular reconstructions induce rheological changes in the anastomosed vessels and are usually counteracted by anticoagulative medication. There is no regimen commonly agreed on. This study provides an easy to use anticoagulative regimen. PATIENTS AND METHODS: Consecutive cases of either anticoagulative regimen between 2013 and 2018 that underwent microvascular reconstruction in the head and neck area were included in this retrospective study, resulting in 400 cases in total. Two different anticoagulative regimens were applied to 200 patients in each group: (a) intraoperatively administered unfractionated 5000 I.U. high molecular weight heparin (HMWH) and postoperatively low molecular weight heparin (LMWH, Enoxaparin) 1 mg/kg/body weight postoperatively and (b) intraoperatively LMWH 0.5 mg/kg/body weight as well as 12 h later and 1 mg/kg/body weight postoperatively. RESULTS: The LMWH cohort showed fewer overall thromboembolic (8.5% vs. 11%; p = .40) and peripheral thrombotic events (1% vs. 3.5%; p = .18) and lung embolisms (3% vs. 4%; p = .59). The number of thromboses at the site of the anastomosis was equally distributed. In regard to flap-specific complications, LMWH was associated with a positive effect, in particular with respect to total flap losses (5% vs. 7%; p = .40) and wound-healing disorders (14.5% vs. 20%; p = .145). CONCLUSION: Findings indicate that intra- and postoperatively administered LMWH as the only anticoagulative medication seems reliable in our clinical routine of head and neck free flap reconstructions.

The impact of passive alveolar molding vs. nasoalveolar molding on cleft width and other parameters of maxillary growth in unilateral cleft lip palate.

OBJECTIVE: Passive alveolar molding (PAM) and nasoalveolar molding (NAM) are established presurgical infant orthodontic (PSIO) therapies for cleft lip palate (CLP) patients. PAM guides maxillary growth with a modified Hotz appliance, while NAM also uses extraoral taping and includes nasal stents. The effects of these techniques on alveolar arch growth have rarely been compared. MATERIAL AND METHODS: We retrospectively compared 3D-scanned maxillary models obtained before and after PSIO from infants with unilateral, non-syndromic CLP treated with PAM (n = 16) versus NAM (n = 13). Nine anatomical points were set digitally by four raters and transversal/sagittal distances and rotations of the maxilla were measured. RESULTS: Both appliances reduced the anterior cleft, but NAM percentage wise more. NAM decreased the anterior and medial transversal width compared to PAM, which led to no change. With both appliances, the posterior width increased. The alveolar arch length of the great and small segments and the sagittal length of the maxilla increased with PAM but only partially with NAM. However, NAM induced a significant greater medial rotation of the larger and smaller segment compared to PAM with respect to the lateral angle. CONCLUSIONS: NAM and PAM presented some significant differences regarding maxillary growth. While NAM reduced the anterior cleft and effectively rotated the segments medially, PAM allowed more transversal and sagittal growth. CLINICAL RELEVANCE: The results of this study should be taken into consideration when to decide whether to use PAM or NAM, since they show a different outcome within the first few months. Further studies are necessary regarding long-term differences.

Imaging of traumatic mandibular fractures in young adults using CT-like MRI: a feasibility study.

OBJECTIVES: To assess and compare the diagnostic performance of CT-like images based on a three- dimensional (3D) T1-weighted spoiled gradient-echo sequence (3D T1 GRE) with CT in patients with acute traumatic fractures of the mandible. MATERIALS AND METHODS: Subjects with acute mandibular fractures diagnosed on conventional CT were prospectively recruited and received an additional 3 T MRI with a CT-like 3D T1 GRE sequence. The images were assessed by two radiologists with regard to fracture localization, degree of dislocation, and number of fragments. Bone to soft tissue contrast, diagnostic confidence, artifacts, and overall image quality were rated using a five-point Likert-scale. Agreement of measurements was assessed using an independent t-test. RESULTS: Fourteen subjects and 22 fracture sites were included (26 ± 3.9 years; 4 females, 10 males). All traumatic fractures were accurately detected on CT-like MRI (n = 22, κ 1.00 (95% CI 1.00-1.00)). There was no statistically significant difference in the assessment of the fracture dislocation (axial mean difference (MD) 0.06 mm, p = 0.93, coronal MD, 0.08 mm, p = 0.89 and sagittal MD, 0.04 mm, p = 0.96). The agreement for the fracture classification as well as the inter- and intra-rater agreement was excellent (range κ 0.92-0.98 (95% CI 0.96-0.99)). CONCLUSION: Assessment of mandibular fractures was feasible and accurate using CT-like MRI based on a 3D T1 GRE sequence and is comparable to conventional CT. CLINICAL RELEVANCE: For the assessment of acute mandibular fractures, CT-like MRI might become a useful alternative to CT in order to reduce radiation exposure particularly in young patients.

Blood flow analyses by intraoperative transit-time flow measurements of free flaps for head and neck reconstructions: A prospective single-center study.

BACKGROUND: The behavior of blood flow changes within free flaps following microvascular anastomosis is not well described in the literature. The aim of this study was to determine the immediate blood flow behavior of different free flaps as reference values for various clinical applications. METHODS: Intraoperative transit-time flow measurements were performed on patients receiving free flap transfer in the head and neck area comprising radial forearm flaps (RFF), peroneal artery perforator flaps (PAP), anterolateral thigh flaps (ALT), vastus lateralis flaps (VLF), parascapular flaps (PSF), latissimus dorsi flaps (LDF), fibula free flaps (FFF), deep circumflex iliac artery flaps (DCIA), and scapular flaps (SF). In accordance with a structured protocol, measurements took place at the pedicle directly before flap harvesting and at the recipient vessels 1 h after flap transfer. Heart rate, transplant weight, and other patient characteristics were recorded and analyzed. RESULTS: A total of 129 were enrolled, comprising 66 RFF, 8 ALT, 6 PAP, 11 VLF, 3 PSF, 2 LDF, 24 FFF, 7 DCIA, and 2 SF. In most of the transplant groups, arterial perfusion increased after anastomosis at the recipient site. The arterial pulsatility index developed indirectly proportionally to arterial blood flow, whereas venous blood drainage did not show any statistically significant changes. Muscle flaps had the highest arterial perfusion before flap transfer. Composite transplants with hard and soft tissue presented the greatest increase in arterial perfusion. The lowest arterial blood flow after anastomosis was measured in PAP and RFF. In contrast, RFF and PAP presented the highest arterial perfusion per 100 g transplant weight. CONCLUSIONS: Arterial perfusion changed, whereas venous blood flow did not show any statistically significant variations in any transplant group. Perfusion of free flaps does not only depend on the recipient vessel and the recipient bed, but also on flap-specific anatomy and physiology.

Factors Associated With Postoperative Delirium in Patients Undergoing Complex Head and Neck Flap Surgery.

PURPOSE: Postoperative delirium (PD) is a common and severe complication, following extensive surgery and prolonged stays in intensive care units (ICU). The study aimed to estimate the frequency of and identify risk factors for PD in a unified sample of head and neck surgery patients. METHODS: The investigators implemented a retrospective cohort study composing of patients undergoing free flap reconstructive surgery over 1 year. The predictor variables were identified as 146 general and periprocedural parameters. The primary outcome variable was PD (+ or -). Descriptive and bivariate statistics were performed to identify existing correlations between the predictive factors and PD and the P-value was set at .05. A logistic regression model (LRM) was created to adjust for possible confounding factors and reveal possible independent prognostic factors for the onset of PD. RESULTS: Hundred patients (group 1, 18 with PD+, group 2, 82 without PD) undergoing microvascular free flap (65 males, 35 females, mean age = 65 [range 18 to 84 years]) surgery were recruited. The investigators identified 15 variables that were statistically associated with PD. In the LRM, after adjusting for age, diabetes status, and preoperative TSH, free fibula transplants (FT) as type of surgery was associated with an increased risk for PD (FT, Odds Ratio (OR) 6.3 (1.6 to 25.7, P = .01). CONCLUSION: The investigators identified 15 variables associated with an increased risk of developing PD, one of which had a statistically significant association after adjusting for other variables in a LRM. Future research efforts should be devoted to assessing the use of these variables for predicting PD further. Since the use of FT showed to be an independent prognostic parameter for the development of PD in this study, patients receiving FT should get special attention in the first days after surgery to prevent PD and associated complications such as increased mortality and prolonged hospital stays.

Composition and Clinical Impact of the Immunologic Tumor Microenvironment in Oral Squamous Cell Carcinoma.

Immunotherapy shows promising results and revolutionizes treatment of oral squamous cell carcinoma (OSCC). The immunologic microenvironment might have prognostic/predictive implications. Morphologic immunologic parameters (inflammatory infiltrate, stromal content, and budding activity [BA] [potentially indicating epithelial-mesenchymal transition]) were evaluated in 66 human primary therapy-naive OSCCs. Intraepithelial/stromal tumor-infiltrating lymphocytes (TILs; CD3+/CD4+/CD8+/CD4+FOXP3+/IL-17A+) were quantified, and ratios were calculated. HLA class I in tumor cells was evaluated immunohistochemically. mRNA in situ hybridization to detect IFN-γ was performed. Analysis was performed within invasive front (IF) and tumor center (TCe). Decreased HLA expression was associated with low TIL density, pronounced stromal content, and high BA; IFN-γ in TILs was correlated with high-density TILs; and IFN-γ in tumor cells was correlated with absence of BA (p < 0.05). Heterogeneity of parameters (TCe/IF) was rare. Low density of stromal CD4+FOXP3+ TILs within TCe and IF was identified as an independent prognostic factor for poor overall, disease-specific, and disease-free survival (p ≤ 0.011). Refining prognostication in OSCC with high-density CD4+FOXP3+ infiltrate within TCe and/or IF, high FOXP3:CD4 ratio was significantly correlated with favorable outcome in this subgroup. Furthermore, high-stromal CD8:CD4 ratio was found to be an independent favorable prognostic factor. In summary, immunologic parameters were closely intertwined. Morphologic correlates of epithelial-mesenchymal transition were associated with downregulation of HLA and decreased inflammation. Heterogeneity was infrequent. Low-density stromal CD4+FOXP3+ infiltrate within TCe and IF was an independent poor prognostic factor. Stratification of cases with high-density CD4+FOXP3+ TILs by FOXP3:CD4 ratio enables refinement of prognostication of this subgroup. CD8:CD4 ratio was identified as an independent prognostic factor.

Is There a Significant Difference in Relapse and Complication Rate of Surgically Assisted Rapid Palatal Expansion Using Tooth-Borne, Bone-Borne, and Orthodontic Mini-Implant-Borne Appliances?

PURPOSE: For surgically assisted rapid palatal expansion (SARPE), studies comparing different devices are missing. The aim was to evaluate expansion, relapse, and the complication rates for 3 different appliances. PATIENTS AND METHODS: In this retrospective cohort study, tooth-borne (TB, n = 29), bone-borne (BB, n = 12), or orthodontic mini-implant (OMI)-borne (n = 13) appliances were used for SARPE in 2 clinical centers. Patients presenting with a maxillary width discrepancy greater than 5 mm were included. Measurements of cast models and radiographs were performed preoperatively, immediately after consolidation, and at 1 year postoperatively. All distances were measured between canines, premolars, and molars. Complications (tooth damage, infection, technical failure) were evaluated. The outcome variables were expansion, relapse, and complications. Type of appliance was selected as predictor variable. Within- and between-group differences regarding expansion, relapse, and complications for the 3 appliances were statistically analyzed. RESULTS: In 54 patients (aged 28.8 ± 8.6 years), mean expansion (±standard deviation) for the TB, BB, and OMI appliances immediately after consolidation was 5.29 ± 1.39 mm, 5.22 ± 1.72 mm, and 3.81 ± 2.19 mm, respectively, at the dental level, and 5.51 ± 1.40 mm, 4.66 ± 2.03 mm, and 3.51 ± 1.66 mm, respectively, at the bone level. Mean (±standard deviation) relapse for the TB, BB, and OMI appliances at 1 year postoperatively measured 1.44 ± 1.01 mm, 0.76 ± 1.37 mm, and 0.27 ± 1.63 mm, respectively, at the tooth level and 1.19 ± 0.93 mm, 0.71 ± 0.96 mm, and 0.12 ± 1.56 mm, respectively, at the bone level. Analysis of variance and the Tukey test showed significant differences between the TB and OMI appliances for expansion and relapse (P = .034 and P = .024, respectively). The overall complication rate differed significantly (P < .001), with rates of 17.2%, 66.7%, and 15.4% for the TB, BB, and OMI appliances, respectively. CONCLUSIONS: BB and OMI appliances resulted in less relapse. Owing to the high complication rate, the further use of BB appliances is questionable.

The impact of intraoperative frozen section analysis on final resection margin status, recurrence, and patient outcome with oral squamous cell carcinoma.

BACKGROUND: The objective of this study was to evaluate the diagnostic value of intraoperative frozen section analysis (IFSA) of tumor bed margins in patients with oral squamous cell carcinoma (OSCC). METHODS: This retrospective study includes 194 primary OSCC cases. The impact of intraoperative information by IFSA on final margin status, local recurrence, and disease-specific survival were analyzed. RESULTS: IFSA revealed a 50% sensitivity and a 100% specificity, with a positive and negative predictive value of 100% and 89.1%, respectively. In 19 cases, margins were rated positive by IFSA and remained positive in eight cases (42.1%), despite immediate re-resection. This constellation led to higher recurrence and lower survival rates than in cases with consecutive R0 status (each p = 0.046). Positive margins in IFSA were associated with closer final margins (p = 0.022) and early recurrences (p = 0.050). CONCLUSIONS: Achieving instant R0 status has a crucial impact on disease recurrence and patient survival. IFSA falls short to ensure secure definite surgical margins. Thus, improved intraoperative diagnostic information on the location and extent of OSCC could support patient treatment. CLINICAL RELEVANCE: Considering that patient survival has not improved despite progress in surgical and adjuvant therapy, the process and outcome of IFSA was scrutinized as one part of the treatment concept.

Retrospective analysis of complications in 190 mandibular resections and simultaneous reconstructions with free fibula flap, iliac crest flap or reconstruction plate: a comparative single centre study.

OBJECTIVES: The purpose of this study was to evaluate the incidence of complications following mandibular reconstruction and to analyse possible contributing factors. MATERIALS AND METHODS: Clinical data and computed tomography scans of all patients who needed a mandibular reconstruction with a reconstruction plate, free fibula flap (FFF) or iliac crest (DCIA) flap between August 2010 and August 2015 were retrospectively analysed. RESULTS: One hundred and ninety patients were enrolled, encompassing 77 reconstructions with reconstruction plate, 89 reconstructions with FFF and 24 reconstructions with DCIA flaps. Cutaneous perforation was most frequently detected in the plate subgroup within the early interval and overall (each p = 0.004). Low body mass index (BMI) and total radiation dosage were the most relevant risk factors for the development of analysed complications. CONCLUSIONS: Microvascular bone flaps have overall less skin perforation than reconstruction plates. BMI and expected total radiation dosage have to be respected in choice of reconstructive technique. CLINICAL RELEVANCE: A treatment algorithm for mandibular reconstructions on the basis of our results is presented.

NAM-help or burden? Intercultural evaluation of parental stress caused by nasoalveolar molding: a retrospective multi-center study.

OBJECTIVES: Nasoalveolar molding (NAM) was developed to facilitate easier treatment and better outcomes for cleft lip and palate (CLP) patients. The aim of this study was to investigate the parental burden and possible intercultural differences of this treatment modality, which is often argued to burden parents to an extraordinary amount. MATERIALS AND METHODS: Standardized questionnaires (available in English, Mandarin, and German) with 15 non-specific and 14 NAM-specific items to be retrospectively answered by Likert scales by parents of unilateral CLP patients with completed NAM treatment. RESULTS: The parents of 117 patients from two treatment centers in Taiwan and Germany were included. A very high level of overall satisfaction was found in both countries with significant intercultural differences in prenatal parent information, feeding problems, dealing with 3rd party's perception, and experienced personal effort. CONCLUSION: NAM is an effective treatment tool for children's CLP deformities and their caregivers in overcoming the feeling of helplessness. Intercultural differences may be due to infrastructural reasons, cultural attitudes and habits, or different public medical education. CLINICAL RELEVANCE: In addition to facilitating easier surgical treatment, NAM can be seen as a powerful coping strategy for parents dealing with a CLP deformity of their child and does not seem to burden them extraordinarily.

Oxidative and Nitrosative Stress in Oral Squamous Cell Carcinoma.

INTRODUCTION: The incidence of oral squamous cell carcinoma (OSCC) shows a constant increase, while the long-term outcome remains poor over the last decades. Radical oxygen and nitrogen species (RONS) - initially released by carcinogens, such as alcohol and tobacco, and later maintained by the tumor microenvironment - appear to be strongly associated to chronic inflammation, tumor induction, progression, and metastatic spread. The aim of this study was to evaluate the role of oxidative and nitrosative stress in primary OSCC compared to healthy tissue specimens and to identify their impact on tumor carcinogenesis. MATERIALS AND METHODS: In this basic research study, tissue samples of 30 patients with primary OSCC were evaluated for the expression of pAKT, pERK, 3-NT, NOS1, NOS3, MAPK1, and IP-8 by immunohistochemistry and RT-PCR and compared to those of a healthy control group (n = 30). RESULTS: The results showed a significantly increased expression of pAKT (p < 0.001), pERK (p = 0.01), 3-NT (p = 0.039), NOS1 (p = 0.025), NOS3 (p = 0.046), and MAPK1 (p = 0.032) in OSCC tissue samples compared to healthy controls. CONCLUSION: The results of this study prove the tested stable degradation products to be suitable for the detection of RONS in OSCC. Moreover, the significantly increased expression underlines the role of RONS in carcinogenesis of OSCC, suggests specific mechanisms of detection, and anticipates supplementary research.

Development of a template tool for facilitating fibula osteotomy in reconstruction of mandibular defects by digital analysis of the human mandible.

OBJECTIVES: Mandibular reconstruction after segmental mandibulectomy can be challenging without virtual surgical planning and osteotomy guides. The purpose of this study was to analyze anatomic parameters to facilitate the evaluation of ideal fibula wedge osteotomies to reconstruct the neomandibula in a simple and cost-effective manner without the need for preoperative virtual planning. MATERIALS AND METHODS: Computed tomography scans were acquired from randomly selected patients, and all images were obtained from routine clinical diagnostics, e.g., tumor staging, or preoperatively before reconstruction. Data was used to calculate stereolithographic models of the mandible for length and angle measurements. Statistical analysis was performed (p < 0.05). RESULTS: CT scans of 100 patients were analyzed: 39 were female and 61 were male patients, mean age was 59.08a. The mandibular arch angle proved to be constant with 241.07 ± 2.39°. The outside B-segment length was 80.05 ± 5.16 mm; the anterior S-segment length was 27.69 ± 3.16 mm. The angle of the mandibular arch showed differences in means (p = 0.004) between age groups, but effect was proved low. No relevant statistical significances were detected. CONCLUSIONS: The development of a mandible reconstruction template tool would benefit the majority of head and neck patients, which is due to a constant mandibular arch angle and symphysis segment length throughout the general patient population, allowing the mimicking of a harmonic mandibular arch with up to three fibula segments. CLINICAL RELEVANCE: The developed mandible reconstruction template tool can facilitate the fibula wedge osteotomies necessary for reconstruction of an ideal neomandibula providing a novel approach which is simple and cost-effective.

Comparison between Different Perforator Imaging Modalities for the Anterolateral Thigh Perforator Flap Transfer: A Prospective Study.

BACKGROUND: Perforator imaging is routinely performed before perforator flap harvest. Hand-held Doppler (hhD) and color duplex ultrasonography (CDU) are currently the most popular radiation-free methods for this purpose that can be applied by the surgeon alone. The aim of this study was to compare the accuracy, reliability, and feasibility of hhD and CDU with indocyanine green angiography (ICGA) in the anterolateral thigh perforator flap (ALTPF). METHODS: All consecutive ALTPF procedures between May 2017 and April 2018 were included in this prospective study. The perforators were visualized by three investigators independently and randomized, applying hhD, CDU, and ICGA. The presence and the distance to the identified perforator were registered. Further, body mass index (BMI), American Society of Anesthesiologists-status, and the patient's history regarding smoking, alcohol use, and diabetes mellitus were registered alongside gender and age to analyze possible confounders. RESULTS: A total of 12 patients were enrolled with a median age of 67 (52-87) years. In total, 30 perforators were detected intraoperatively as well as with the ICGA. The latter visualized the perforators significantly more precisely than hhD and CDU (p < 0.001 and p = 0.001). The sensitivity and positive predictive value were 67 and 62% for hhD, 73 and 64% for CDU, and 100 and 100% for ICGA, respectively. CONCLUSION: According to this study, ICGA visualized perforators more accurately than the standard methods hhD and CDU. Further, it was associated with the highest sensitivity and positive predictive value. ICGA consistently delivered excellent results, whereas hhD and CDU showed variability.

Effect of Segment Length and Number of Osteotomy Sites on Cancellous Bone Perfusion in Free Fibula Flaps.

BACKGROUND: Indocyanine green (ICG) videoangiography is routinely used to evaluate skin and organ perfusion and to assess patency rates of microvascular anastomoses. This study uses ICG angiography as a novel approach to qualitatively and quantitatively evaluate bone perfusion of microvascular fibula grafts intraoperatively and to assess the effect of fibula segment length and number of osteotomies on bone perfusion. METHODS: All patients planned for mandible reconstruction using a microvascular fibula graft between January 2013 and May 2017 were considered for this study. ICG videoangiography of cancellous bone perfusion was performed using a handheld ICG camera. Videos were analyzed, and a perfusion curve was generated. Peak enhancement, time to peak, slope, and wash-in area under the curve were extracted; rise time, wash-in rate (WiR), and wash-in perfusion index were calculated. Results were statistically analyzed with regard to distal fibula segment length and number of osteotomy sites. RESULTS: Thirty-nine patients (age 59 ± 8 years) were included in the study. Mandible reconstruction was achieved with 1 (n = 15), 2 (n = 13), or 3 (n = 11) fibula segments. The WiR was 6.4 ± 2.3 and 4.4 ± 0.2 before and after proximal osteotomy, respectively. The wash-in perfusion index was 114.2 ± 48.4 before and 84.4 ± 20.0 after proximal osteotomy. Bone perfusion was significantly reduced after additional proximal osteotomies. Both the segment length and number of proximal osteotomies correlated with bone perfusion, with longer segments and fewer osteotomies showing higher perfusion. CONCLUSION: This study demonstrates the feasibility of cancellous bone perfusion analysis using ICG and can serve as a basis for future bone perfusion studies. Additional osteotomies and short segment length negatively affects cancellous bone perfusion of the distal fibula segment in free fibula flaps. The extent to which the observed decrease in arterial inflow to the distal fibula segment affects the further course of healing needs to be addressed in future studies.

Immunohistochemical expression of CD44 in oral squamous cell carcinoma in relation to histomorphological parameters and clinicopathological factors.

AIMS: Oral squamous cell carcinoma (OSCC) is characterised by its variable clinical course. In addition to the routinely used TNM and Union for International Cancer Control systems, patient-specific prognostic/predictive biomarkers are needed. Promising biomarkers include the determination of the cancer stem cell compartment, which can be identified by CD44 expression (among other things). The aim of this study was to evaluate the impact of CD44 in OSCC in terms of correlation with histomorphology, especially targeting features of EMT, and its influence on patient prognosis. METHODS AND RESULTS: A well-characterised cohort of 108 therapy-naive OSCCs with complete long-term follow-up and matched lymph node metastases were evaluated for CD44 expression by immunohistochemistry. CD44 expression was correlated with histomorphological characteristics (including tumour differentiation and tumour budding), clinicopathological parameters, and follow-up data. Overexpression of CD44 was detected in 37% of OSCCs within the tumour centre, in 39% of OSCCs at the invasive margin, and in 16% of lymph node metastases. CD44 overexpression at the invasive margin was significantly correlated with poor histopathological differentiation, and specifically with high tumour budding activity and single-cell invasion as signs of epithelial-mesenchymal transition (EMT). CD44 overexpression within the tumour core region and in lymph node metastases was identified as an independent prognostic factor for poor overall, disease-specific and disease-free survival in subsets of patients with advanced OSCC. CONCLUSION: Our study demonstrates the association of CD44 with tumour aggressiveness and EMT, as well as the independent prognostic impact of CD44 in a subset of OSCCs, which underlines the role of tumour cell stemness as a key factor in malignant behaviour in this disease.

Tumour budding activity and cell nest size determine patient outcome in oral squamous cell carcinoma: proposal for an adjusted grading system.

AIMS: Oral squamous cell carcinoma (OSCC) is a common malignancy with a variable clinical course. One of the established survival predictors in carcinomas in general is tumour grade; in OSCC, however, grading according to the World Health Organization (WHO) has no independent prognostic impact. Recently, a novel grading scheme associated with high impact on patient outcome has been proposed for squamous cell carcinoma of the lung. METHODS AND RESULTS: To probe whether this scheme could be applied to the upper aerodigestive tract, we retrospectively evaluated 157 chemo- and radiotherapy-naive OSCCs with complete clinical follow-up data and standardized treatment for tumour budding activity (BA), cell nest size (CNS), extent of keratinization, stromal content, nuclear size and mitotic count. Histomorphological characteristics were correlated with clinicopathological data and patient outcome. As in squamous cell carcinoma of the lung, high BA and small CNS were correlated significantly with shortened overall, disease-specific and disease-free survival. A three-tiered grading system based on a sum score of these two prognostic markers proved to be a strong age-, stage- and sex-independent prognosticator for survival with a hazard ratio for overall survival of 2.1 for intermediately differentiated (G2) tumours and 3.4 for poorly differentiated (G3) tumours compared to well-differentiated (G1) tumours (P < 0.001). CONCLUSIONS: We recapitulated and validated almost exactly the strong prognostic impact of a grading algorithm proposed recently for squamous cell carcinoma of the lung in OSCC. Our data may pave the way for a prognostically highly relevant future squamous cell carcinoma grading system broadly applicable in the aerodigestive tract.

An Immunohistochemical Study on the Role of Oxidative and Nitrosative Stress in Irradiated Skin.

BACKGROUND/AIM: The effects of ionizing radiation through the generation of free radicals, reactive aldehydes, and other oxidative and nitrosative by-products account for skin injuries as side effects of radiation therapy (RT). This study aims to identify cellular pathways in oxidative and nitrosative stress in irradiated skin using well-established marker proteins in an immunohistochemical analysis. MATERIALS AND METHODS: Tissue specimens of 51 patients were obtained during operative access to the neck. Twenty patients (39.2%) received RT prior to the surgical intervention. Immunohistochemical analysis of stable degradation products of reactive oxygen and nitrogen species (RONS), 3-nitrotyrosine, 8-isoprostane, phosphorylated AKT (p-AKT), and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed in specimens which were exposed to RT and those without a history of RT. RESULTS: Immunohistochemical staining showed a significantly increased expression of nitrotyrosine in superficial and basal epidermal regions of interest (ROI), p-AKT in all epidermal ROI, and p-ERK in all the investigated epidermal and dermal ROI, as well as in an overall analysis. No significance could be detected in immunostaining against isoprostane. DISCUSSION: This study summarizes the influence of RONS in RT. Moreover, a detailed histological analysis was able to identify epidermal ROI as a main starting point of RONS in irradiated skin. Even though the role of RONS in high-dose therapeutic radiation remains a subject for further research, these data underlines the crucial role of RONS in high-dose radiation.

Comparative 3D micro-CT and 2D histomorphometry analysis of dental implant osseointegration in the maxilla of minipigs.

AIM: The bone implant contact (BIC) has traditionally been evaluated with histological methods. Thereupon, strong correlations of two-dimensional (2D) BIC have been detected between µCT and destructive histology. However, due to the high intra-sample variability in BIC values, one histological slice is not sufficient to represent 3D BIC. Therefore, our aim has been to correlate the averaged values of 3-4 histological sections to 3D µCT. MATERIAL AND METHODS: Fifty-four implants inserted into the maxilla of 14 minipigs were evaluated. Two different time points were selected to assess the 3D BIC (distance to implant: 2-5 voxels), an inner ring (6-30 voxels) and an outer ring (55-100 voxels) using µCT (voxel size: 10 µm) and to correlate the values to histomorphometry. RESULTS: Strong correlations (p < 0.0001; 28 days, 56 days, total) were seen between µCT and histomorphometry concerning BIC (r = 0.84, r = 0.85, r = 0.83), the inner ring (r = 0.87, r = 0.87, r = 0.88) and the outer ring (r = 0.85, r = 0.85, r = 0.88). Closer to the implant, µCT values were higher compared with histomorphometry. CONCLUSION: Although 3-4 histological slices per implant seem to predict the 3D BIC, µCT might be advantageous because of its non-destructive 3D character. The healing time may not impact on the comparability.

Indocyanine green videoangiography-assisted prediction of flap necrosis in the rat epigastric flap using the flow® 800 tool.

BACKGROUND: The decision to re-operate on a potentially ischemic free flap remains challenging. Indocyanine green videoangiography (ICG) with the FLOW® 800 tool is a method which allows an immediate qualitative conclusion about the patency of an anastomosis. Is it also able to predict the outcome of potentially compromised vascular free flaps? MATERIALS AND METHODS: An epigastric flap was raised and repositioned in 79 rats. Intraoperative fluorescence angiography was performed using ICG videoangiography and the FLOW® 800 tool was applied. Six regions of interest were positioned systematically over the flap, changes of the ICG fluorescence were color coded with respect to time and 474 measurements were performed. The flap was clinically monitored for one week and the resulting necrotic areas were correlated with the ICG/FLOW® 800 results. RESULTS: Mean intensity of clinically vital areas was 83.39 ± 50.96 arbitrary units (AU) and 37.33 ± 15.14 AU in necrotic areas. The receiver operating characteristic curve and Youden-Index analysis revealed that the optimal cutoff for the maximal intensity of ICG after FLOW® 800 analysis was ≤ 61.733 for the prediction of flap necrosis and > 61.733 for the prediction of flap survival (P < 0.0001; 95% CI = 0.85-0.91; Youden-Index: 0.67). The maximal intensity of ICG angiography had a specificity of 96.1% and sensitivity of 71.4%. The positive predictive value was 97.46% and the corresponding negative predictive value was 61.34%. CONCLUSION: This demonstrates the potential additional value of ICG videoangiography including FLOW® 800 analyses in the postoperative monitoring of transplanted flaps. © 2016 Wiley Periodicals, Inc. Microsurgery 37:235-242, 2017.

A prospective longitudinal study of postnatal dentoalveolar and palatal growth: The anatomical basis for CAD/CAM-assisted production of cleft-lip-palate feeding plates.

This study describes the dentoalveolar and palatal growth during the first months of life. Knowledge concerning this development is essential to avoid unwanted events such as mucosal ulcerations or restriction of growth when cleft-lip and palate (CLP) patients are treated. The results involve the generation of CAD/CAM CLP-feeding plates. Intraoral impressions from 32 healthy newborns were taken monthly for 5 months, supplemented by measurements of body weight, length, and occipital-frontal head circumference. The casts were digitalized, and two observers manually selected defined anatomical landmarks on virtual 3-D models. The distances between these landmarks were evaluted. Statistical analysis included an inter-rater agreement analysis and the determination of growth. In total, 213 casts were analyzed, with 65 models excluded because of inaccuracies in impression-taking or cast production. Overall longitudinal growth was 20.3%, whereas transversal growth reached a maximum of 21.1%. Vertical growth was 32.4% at the tuberal level. On the basis of these results, a semiautomated series of feeding plates allowing for monthly expansion could be generated. The acquired data serve as a useful reference for other pediatric and orthofacial investigations and treatments. One such application is the automated, fully virtual manufacture of CLP-feeding plates based on only one impression-taking. Our data reveal when caution is needed to prevent ulceration. The series of plates generated can minimize the time-consuming impression-taking and the production of further plaster models. The method of measurement is suitable for documentary purposes. Clin. Anat. 30:846-854, 2017. © 2017 Wiley Periodicals, Inc.